Cervical cancer is one of the most common cancers among women worldwide. Approximately 500,000 new cases are diagnosed each year, resulting in over 200,000 deaths. Infection with one of a dozen or so oncogenic HPV types is now known to be the cause of nearly all cervical tumors, with two HPV types, HPV16 and HPV18, accounting for approximately 70% of the cases worldwide. Although cytological screening programs have been in place for several decades, these programs have not been effective at controlling cervical cancer in developing countries, where the vast majority of cervical cancer cases are diagnosed. Costa Rica was chosen for the Phase 3 trial because of our extensive successful scientific collaborations there, the high risk of cervical cancer, the universal medical system providing national linkage, and the likelihood of very high participation over the many needed years of close clinical follow-up. Randomization and 3-dose vaccination of 7,466 women enrolled into the HPV-16/18 Vaccine Trial in Costa Rica has been successfully completed. Women have been followed actively on an annual or semi-annual basis since enrollment. Women are now completing their first four years of follow-up in the trial and are being asked to enroll in the extended (up to 10 years) follow-up phase of the study. As women complete four years of active follow-up, cross-over vaccination is offered to trial participants. To date, the trial remains masked. Initial analyses focused on efficacy against virological outcomes are planned and the primary analysis of the prophylactic effect of this vaccine against histological endpoints is expected at the end of the first 4-years of follow-up. Evaluation of the therapeutic benefit of this vaccine has been completed. Results from the analysis indicate that the vaccine does not have any effect on clearance of HPV infections, when administered to women who already have an established infection. Thus, the vaccine should not be used to treat established infections and confers maximum benefit when administered to adolescents prior to sexual debut.